Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats.
Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats.
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DOI：
10.1002/jnr.22483
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发表时间：
2010-11-15
影响因子：
4.2
通讯作者：
Li, Yu-Long
中科院分区：
文献类型：
--
作者：
Tu, Huiyin;Zhang, Libin;Tran, Thai P.;Muelleman, Robert L.;Li, Yu-Long
电压门控钠（Nav）通道负责神经元中动作电位的起始和传播。为探讨慢性心力衰竭（CHF）引起的压力感受器反射功能障碍的机制，我们检测了假手术和CHF大鼠主动脉压力感受器神经元Nav1.7、Nav1.8和Nav1.9亚单位的表达和电流密度，并研究了Nav1.7、Nav1.8和Nav1.9通道对主动脉压力感受器神经元兴奋性和压力感受器反射敏感性的作用。左冠状动脉结扎致CHF。通过血流动力学和形态学特征证实CHF的发展（冠状动脉结扎后6-8周）。免疫荧光结果显示Nav1.7在A型（有髓）和C型（无髓）结状神经元中表达，而Nav1.8和Nav1.9仅在C型结状神经元中表达。实时荧光定量RT-PCR和蛋白质印迹结果显示，CHF降低了结状神经元Nav通道mRNA和蛋白质的表达水平。此外，采用全细胞膜片钳技术，我们发现CHF大鼠主动脉压力感受器神经元的Nav电流密度和细胞兴奋性低于假手术大鼠。麻醉CHF大鼠主动脉压力感受性反射敏感性较假手术组减弱。此外，Nav通道激活剂（rATX II，100 nM）显着增加主动脉压力感受器神经元的Nav电流密度和细胞兴奋性，并改善主动脉压力感受器反射敏感性在CHF大鼠。这些结果表明，在CHF状态下，Nav通道的表达和激活减少参与了压力感受器神经元兴奋性的衰减，从而导致压力感受器反射受损。
Voltage-gated sodium (Nav) channels are responsible for initiation and propagation of action potential in the neurons. To explore the mechanisms for chronic heart failure (CHF)-induced baroreflex dysfunction, we measured the expression and current density of Nav channel subunits (Nav1.7, Nav1.8, and Nav1.9) in the aortic baroreceptor neurons and investigated the role of Nav channels on aortic baroreceptor neuron excitability and baroreflex sensitivity in sham and CHF rats. CHF was induced by left coronary artery ligation. The development of CHF (6–8 weeks after the coronary ligation) was confirmed by hemodynamic and morphological characteristics. Immunofluorescent data indicated that Nav1.7 was expressed in A-type (myelinated) and C-type (unmyelinated) nodose neurons but Nav1.8 and Nav1.9 were expressed only in C-type nodose neurons. Real-time RT-PCR and western blot data showed that CHF reduced mRNA and protein expression levels of Nav channels in nodose neurons. In addition, using the whole cell patch-clamp technique, we found that Nav current density and cell excitability of the aortic baroreceptor neurons were lower in CHF rats than that in sham rats. Aortic baroreflex sensitivity was blunted in anesthetized CHF rats, compared with that in sham rats. Furthermore, Nav channel activator (rATX II, 100 nM) significantly enhanced Nav current density and cell excitability of aortic baroreceptor neurons and improved aortic baroreflex sensitivity in CHF rats. These results suggest that reduced expression and activation of the Nav channels is involved in the attenuation of baroreceptor neuron excitability, which subsequently contributes to the impairment of baroreflex in CHF state.
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影响因子：
10.8
作者：
Li, Yu-Long;Xia, o-Hong Xia;Schultz, Harold D.
通讯作者：
Schultz, Harold D.
影响因子：
2.5
作者：
Ritter, Amy M.;Martin, William J.;Thorneloe, Kevin S.
通讯作者：
Thorneloe, Kevin S.
影响因子：
5.5
作者：
Li, Z;Lee, HC;Abboud, FM
通讯作者：
Abboud, FM
影响因子：
2.9
作者：
CAFFREY, JM;ENG, DL;KOCSIS, JD
通讯作者：
KOCSIS, JD
DOI：
10.1016/0735-1097(93)90466-e
发表时间：
1993-10-01
影响因子：
24
作者：
FLORAS, JS
通讯作者：
FLORAS, JS